Tissue-specific Responses to Influenza Immunization and Their Relation to Blood Biomarkers (SLVP032)

Phase 4

Terminated

• Conditions: Influenza
• Interventions: Biological: FluMist®; Biological: Fluzone®

• Registration Number: NCT03023709
• Lead Sponsor: Stanford University

Brief Summary

The investigators collected blood and lymphoid tissues routinely discarded during surgery from adults after a routine seasonal influenza vaccination to determine how immune memory develops at the actual site of infection, and how immunization may alter this process.

Detailed Description

This is a Phase IV study of licensed influenza vaccines with up to 30 male and female adults, 18-49 years of age that was halted due to the recommendation that live, attenuated influenza vaccine (LAIV) not be used as a seasonal flu vaccine. Volunteers were patients undergoing tonsillectomy for treatment of obstructive sleep apnea (OSA).

In the initial pilot phase of the study, up to 3 volunteers will be enrolled and will receive the current seasonal quadrivalent, inactivated influenza vaccine (IIV4) given intramuscularly to confirm the safety of administering the seasonal influenza vaccine 3-14 days prior to tonsillectomy. Enrollment of the remaining study volunteers into the main portion of the study will begin once the initial pilot phase is completed. All of the remaining study volunteers will be given the current year's quadrivalent, live, attenuated seasonal influenza vaccine (LAIV4) intranasally.

The second study visit for all volunteers will occur at the time of the volunteer's tonsillectomy surgery, 3-14 days after Visit 01. A member of the surgical team will collect a 20 mL blood sample and a sample of the resected tonsil tissue that would otherwise be discarded to be distributed to the lab.

Study Timeline

• Study Start: 2015-09
• Primary Completion: 2015-12
• Study Completion: 2015-12
• Study First Submitted: 2017-01-13
• Study First Submitted QC: 2017-01-13
• Study First Posted: 2017-01-18
• Results First Submitted: 2017-01-19
• Status Verified: 2017-03
• Results First Submitted QC: 2017-03-30
• Last Update Submitted: 2017-03-30
• Results First Posted: 2017-05-10
• Last Update Posted: 2017-05-10

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 3

Inclusion Criteria

1. Generally healthy 18-49 year old male and female patients undergoing tonsillectomy for obstructive sleep apnea.
2. Willing to complete the informed consent process
3. Availability for follow-up for the planned duration of the study
4. Acceptable medical history by review of inclusion/exclusion criteria

Exclusion Criteria

1. Prior off-study vaccination with seasonal influenza vaccine within three months of study vaccination
2. Life-threatening reactions to previous influenza vaccinations
3. Asthma (contraindication for receipt of LAIV4) for study volunteers; not a contraindication for enrolling as a pilot phase volunteer receiving IIV4.
4. Allergy to egg or egg products or to vaccine components (including gentamicin, gelatin, arginine or MSG for participants receiving LAIV4).
5. Active systemic or serious concurrent illness, including febrile illness on the day of vaccination
6. History of immunodeficiency (including HIV infection)
7. Known or suspected impairment of immunologic function; may include significant liver disease, diabetes mellitus treated with insulin or moderate to severe renal disease
8. Hospitalization in the past year for congestive heart failure or emphysema.
9. Chronic Hepatitis B or C.
10. Recent or current use of immunosuppressive medication, including systemic glucocorticoids (corticosteroid nasal sprays and topical steroids are permissible). Use of oral steroids (<20mg prednisone-equivalent/day) may be acceptable after review by the investigator.
11. Participants who care for severely immunosuppressed persons that require a protective environment should not receive LAIV, or should avoid contact with such persons for 7 days after receipt, given the theoretical risk for transmission of the live attenuated vaccine virus to close contacts. [If yes, may be ineligible]
12. Malignancy, other than squamous cell or basal cell skin cancer (includes solid tumors such as breast cancer or prostate cancer with recurrence in the past year, and any hematologic cancer such as leukemia).
13. Autoimmune disease (including rheumatoid arthritis treated with immunosuppressive medication such as Plaquenil, methotrexate, prednisone, Enbrel) which, in the opinion of the investigator might jeopardize volunteer safety or compliance with the protocol.
14. History of blood dyscrasias, renal disease, or hemoglobinopathies requiring regular medical follow up or hospitalization during the preceding year
15. Use of any anti-coagulation medication such as Coumadin or Lovenox, or anti-platelet agents such as aspirin (except up to 325 mg. per day), Plavix, or Aggrenox will be reviewed by investigators to determine if study participation would affect the volunteer's safety or compliance with the protocol.
16. Has taken an influenza antiviral medication within 48 hours prior to study vaccination [For volunteers receiving LAIV; If yes, may not eligible if unable to schedule at an appropriate interval].
17. Receipt of blood or blood products within the past 6 months or planned use during the study.
18. Medical or psychiatric condition or occupational responsibilities that preclude participant compliance with the protocol
19. Receipt of an inactivated vaccine 14 days prior to study enrollment, or planned vaccinations prior to completion of last study visit (~ 14 days after study vaccination)
20. Receipt of a live, attenuated vaccine within 60 days prior to enrollment of planned vaccination prior to completion of last study visit (~ 14 days after study enrollment)
21. Need for allergy immunization (that cannot be postponed) until after the last study visit.
22. History of Guillain-Barré syndrome
23. Pregnant woman;
24. Breastfeeding woman [if volunteer will receive LAIV4]
25. Use of investigational agents within 30 days prior to enrollment or planned use during the study.
26. Donation of the equivalent of a unit of blood within 6 weeks prior to enrollment or donation of platelets within 2 weeks of enrollment or planned donation prior to completion of the last visit.
27. Any condition which, in the opinion of the investigator, might interfere with volunteer safety, study objectives or the ability of the participant to understand or comply with the study protocol.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Study phase	FluMist®	Participants will be given the current year's quadrivalent, live, attenuated seasonal influenza vaccine (LAIV4)/FluMist® intranasally 3-14 days prior to tonsillectomy.
Pilot phase	Fluzone®	Participants will receive the current seasonal quadrivalent, inactivated influenza vaccine (IIV4)/Fluzone® given intramuscularly to confirm the safety of administering the seasonal influenza vaccine 3-14 days prior to tonsillectomy.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Related Adverse Events	Day 0 to 14 post-immunization
Number of Participants Who Received Influenza Vaccine	Day 0